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NASH Studies Unit -NAFLD & NASH Info

Blood tests Click here for the answer: More
Imaging tests Click here for the answer: More
Liver biopsy Click here for the answer: More
Normal Liver

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NASH Liver

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What is fatty liver disease? Click here for the answer: More
What are the symptoms? Click here for the answer: More
Insulin resistance as a cause of NAFLD Click here for the answer: More
What causes insulin resistance? Click here for the answer: More
Who is at greatest risk for developing NAFLD? Click here for the answer: More
Why do some people with NAFLD develop NASH? Click here for the answer: More
Why do some people develop cirrhosis? How fast does this happen? Click here for the answer: More
Why worry? What problems are caused by NAFLD? Click here for the answer: More
What are the treatment options for NAFLD? Click here for the answer: More


Helpful information about NAFLD and NASH


What is fatty liver disease?


NAFLD: When too much fat is present in the liver of someone who doesn’t drink much alcohol, this is called “Nonalcoholic Fatty Liver Disease” or “NAFLD”. A little bit of fat in the liver is normal, but when too much of it accumulates, it can damage the liver.


NASH: When too much fat causes significant damage to the liver, this is called “Nonalcoholic steatohepatitis” or “NASH”. “Steato” means fat and “hepatitis” means inflammation and damage in the liver.


By these definitions, everyone with NASH has NAFLD, but not everyone one with NAFLD has NASH. NASH is the worst type of NAFLD because it can cause scar tissue to build up in the liver to the point of cirrhosis and liver failure.


What are the symptoms?


Most people don’t have any symptoms.


Sometimes NAFLD can cause aching pain in the right side of the upper abdomen.


Fatigue or feeling tired is common, but it is unclear if this is caused by NAFLD.


Insulin resistance as a cause of NAFLD


Most people with NAFLD have “insulin resistance” as the cause of the fat accumulation in the liver.


Insulin is a hormone released by the pancreas and its job is to signal tissues such as muscle to take up glucose (blood sugar) from the bloodstream.


Insulin resistance causes the cells of the body to respond sluggishly to insulin. When this happens, higher blood insulin levels are needed to keep the glucose levels in the proper range. If insulin resistance becomes severe, even high levels of insulin are not enough to get the glucose out of the bloodstream. In this case, glucose levels rise and this is called type 2 diabetes. The important point of this is that insulin resistance causes high levels of insulin in the blood. It is often present for decades before the development of diabetes.


High insulin levels in the blood cause fat to accumulate in the liver in most people. Other causes of NAFLD include some dietary deficiencies, a few medications, and unusual genetic defects.


What causes insulin resistance?


Abdominal obesity (apple shaped body) and sedentary lifestyle are the major causes of insulin resistance.


The genes that you inherited from your parents seem to play a large role too. Current medical research is focused on identifying what those genes are so that prevention and treatment can be tailored to individuals.


Who is at greatest risk for developing NAFLD?


People who are overweight and sedentary are at the greatest risk. This includes children who are overweight and watch TV or play video games for hours each day instead of engaging in regular physical activity.


Why do some people with NAFLD develop NASH?


We don’t know why fat damages the liver in some people.


Some researchers believe that “free radicals” are an important cause, but this has not been proven and experimental trials of antioxidants have not convincingly shown any benefit. Answering this question is an area of active investigation by many researchers around the world right now.


Why do some people develop cirrhosis? How fast does this happen?


About a third of people with any form of chronic liver disease develop excess scar tissue throughout the liver. In some people, this “fibrosis” progresses to the point of cirrhosis.


Cirrhosis means that there is too much scar tissue in the liver; cirrhosis has many causes such as NASH, viruses that infect the liver chronically (hepatitis B and C), alcohol abuse, excess iron in the liver, immune system damage to the liver or bile ducts, and developmental diseases.


The development of cirrhosis is a process that usually takes decades, although some people progress over a period of several years (e.g., children who develop NASH cirrhosis).


Why worry? What problems are caused by NAFLD?


Liver swelling from excess fat accumulation can cause achy pain in the abdomen and this can be severe in some people.


The biggest concern is the development of cirrhosis. This probably occurs in about 10% of people with NASH and can lead to liver failure, death or the need for liver transplantation. Once cirrhosis has developed, complications include internal bleeding (variceal hemorrhage), accumulation of fluid in the abdomen (ascites), and progressively worsening confusion caused by toxins that are not cleared by the liver. There is also a small chance of developing liver cancer once cirrhosis has developed.


Liver transplantation is an option once problems from cirrhosis develop, but obesity and the complications of diabetes may preclude consideration for liver transplantation.


Besides these liver complications of NAFLD, the underlying insulin resistance that caused the NAFLD is also associated with high blood pressure, elevated blood triglycerides (fat), atherosclerosis, heart disease, diabetes, gout, and polycystic ovary syndrome. NAFLD can be the first sign that these other diseases could develop later unless insulin resistance is treated.


What are the treatment options for NAFLD?


No treatment has been convincingly proven to be effective.


Treating insulin resistance offers the best hope since this is the underlying problem in most people.


The best treatment of insulin resistance is increased exercise and weight loss. If you had to choose one over the other, exercise alone appears to be better than weight loss alone. Medications can also be used to treat insulin resistance, but the role of these medications in the treatment of NAFLD is experimental.


You should discuss exercise with your doctor before beginning any program of vigorous aerobic activity.


Portion control is the key to weight reduction. Dietary programs that emphasize portion control (e.g., Weight Watchers) have had the most success. A low carbohydrate diet is probably a good idea, but eating unlimited fat (e.g. the Atkins Diet) seems unwise.


People who exercise regularly and eat breakfast every day are most likely to keep weight off once they have lost it.


How are NAFLD and NASH diagnosed?


Blood tests


“Liver enzymes” (proteins in liver cells that are released into the blood when cells are damaged) are often found to be increased in NAFLD. The most commonly used enzyme tests are “ALT” and “AST”. The normal range is usually 10-40 units per liter for both of these.


People with NAFLD and NASH can have ALT values in the normal range or they can be elevated up to 300-400 U/L. Values can fluctuate and changes may not mean that the liver is getting better or worse. Unfortunately, we don’t have a better blood test to detect and follow NAFLD and NASH.


Insulin resistance can also be estimated with a fasting blood test in which the glucose and insulin levels are both measured. When the two results are multiplied (e.g. glucose of 90 mg/dL times insulin of 7 U/L equals 630), a value less than 700 is normal and a value over 2000 indicates insulin resistance. Values in between may indicate mild insulin resistance, the significance of which is uncertain.


Imaging tests


Ultrasound, CT scan (CAT scan), and MRI are all tests that can detect fat in the liver. MRI is best but it is too expensive to use routinely. Unfortunately, none of these tests can tell if there is inflammation and fibrosis in the liver, so NASH cannot be distinguished from “simple steatosis” (fat without significent liver damage).


Liver biopsy


We often recommend a liver biopsy to confirm a suspected diagnosis of NAFLD and to find out if NASH is present. Studies show that we can be wrong about a quarter of the time if we don’t do a biopsy. Only a biopsy will tell us if there is also scar tissue in the liver.


A liver biopsy is performed by numbing a spot in the skin on the right side of the abdomen and passing a needle in and out of the liver through the numb spot in less than a second. The biggest risk of a biopsy is severe bleeding and we must always weigh this risk against the benefit of confirming the diagnosis and knowing if NASH is present.


The liver under the microscope


Normal Liver

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This is an area of normal liver about the size of a pinhead magnified over 1000 times. The hole in the middle is a vein and the other white areas are capillaries where blood flows next to liver cells. Liver cells are reddish with central blue nuclei. The light blue dots around the vein are normal bundles of collagen. Photo courtesy of Dr. E.M. Brunt.

NASH Liver

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This is the same size area of liver as shown above and demonstrates abnormalities typical of NASH. The round white areas in liver cells are fat droplets. Many of the liver cells are also enlarged and pale. This is called “ballooning”. The blue wispy material surrounding many of the liver cells is excess collagen. This is what is called fibrosis. As fibrosis accumulates even more, it develops into cirrhosis. Photo courtesy of Dr. E.M. Brunt.


The opinions expressed here are those of Dr. Tetri. If you have any concerns or questions, be sure to ask Dr. Tetri or your primary physician. It is especially important to talk with your doctors before beginning any program of strenuous exercise.